Cushing's with Renal Disease
Kidney problems
from Cushing's treatment
Cushing's
and Dog's death from Kidney failure
Cushing's with Renal Disease
Cushing's amended
also see Cushing's
also see Renal Disease
also see Liver enzyme levels
Kidney
problems from Cushing's treatment, Addisonian state
Question: In early Oct. my 141/2 yr. old neutered male
doxie was diagnosed w/Cushing's
Disease. He had all the customary testing i.e. Dex suppression
tests etc. and
the test indicated Pituitary Dependent Cushing's. The vet elected
to start
him on Lysodren.
He was admitted after finishing a 5 day course of this drug
with vomiting and
increased diarrhea-he also has colitis and hypothyroidism so
some diarrhea
was normal- but this was worse. The vet kept him on fluid therapy
for 2 days
before doing labs. On the second day he ordered a chem panel
and found that
his "kidney's were failing". This suprised me as his Bun was
only slightly
elevated before initiation of Lysodren therapy and his Creatinine
had been
normal.
He kept him on fluid for another 48 hrs and his kidney values
improved only
slightly-BUN down to 112. He was discharged to my care on a
low protein diet
and PO4 binders.
We repeated labs a week later and BUN was up to 128 and urine
tests showed he
wasn't concentrating his urine. I was told that Darcy was entering
ESRD and
that the prognosis was not good.
My vet was opposed to giving subq fluid but as I work
in a hospital and have
access to the equipment and had friends with training help I
started giving
him 200ccs of fluid every other day. In addition, I started
him on 5mgs of
Pepcid in the morning.
Initially he was very weak, thin and had lost a great deal of
muscle. Very
soon his appetite improved, he gained wt and got stronger. He
went from
14.25lbs to 16lbs now.
He's had labs repeated and on 11/1 is BUN was 128, 11/19
BUN was 56, 11/19
BUN was 56, 11/26 BUN was 57, 12/2 BUN was 59 and Creatinine
was 1.7. His
last labs were done on 12/30 and showed a BUN of 21 and a Creatinine
of 1.2.
Darcy did have a bout of pneumonia in November due, I believe,
to aspiration
of the liquid aluminum hydroxide I was giving him by syringe.
He responded
well to the antibiotics and his WBCs were normal on his last
CBC. I have
since found an aluminum hydroxide product in tablet form so
I no longer risk
using the liquid.
I should also add that Darcy was started on Epogen because
of low PCV. This
has improved enough so that I have cut way back on the Epogen
for fear of
increasing his PCV too much too fast.
My questions are:
When should I next have him tested? My vet is sometimes reluctant
to do labs
-and I don't need unnecessary expense-taking the leave well
enough alone
approach but Darcy's made such good progress I don't want to
let anything
realistically treatable slide. What is a responsible schedule
for testing and
rechecks while all is going well?
Is it possible that his kidney's were so "insulted" by the Lysodren
that they
failed but by so aggressively supporting them we've allowed
them to recover?
Could it be that this is not primary kidney disease after all
and that if I
get him through this he will no longer have kidney disease?
I've read that
kidney disease is not reversible and is always progressive.
What could
account for the improvement in his lab values?
What do I do about the Cushing's Disease? We've all but forgotten
about that
during the this time and I certainly don't want to put him thru
any more Dex
tests. Would Anipryl be risky? His hair has almost all come
back since the
Cushing's diagnosis and his water consumption and peeing are
normal when you
consider the subq fluid. He used to get me up 3-4 times per
night to drink
and pee and now usually sleeps thru the nite.
He's started itching lately. I know there are may possible causes
but do you
have any suggestions? The vet prescribed Atarax but that caused
agitation and
disorientation and I stopped it. He's on so many meds that I
don't know how
to distinguish between and allergic rxn and a skin disease.
I don't see
anything abnormal but there are some rough spots on his chest.
I've read
about a condition called calcinosis cutis-Darcy takes calcium
carbonate on an
alternating basis w/ the aluminum hydroxide as PO4 binders-could
that be the
cause? If it is ,is the condition dangerous?
Sorry for going on so long but I love this dog alot and have
worked very hard
to get him through this. I'm afraid I'll overlook something
simple. I know he
won't live forever but I do want him to have as much quality
time as
possible. Other than these recent catastrophes, he's been doing
remarkably
well and enjoying his life.
Thanks for your help. Donna
Answer: Donna-
I think that there is a good chance that the kidney problems were due
to the treatment for Cushing's
disease. Approximately 5% of dogs treated with mitotane (Lysodren Rx)
develop side effects
consistent with hypoadrenocorticism (Addison's disease). This requires
supplementation with either
glucocorticoids or mineralocorticoid medications to prevent adverse
effects, including kidney failure.
If there was an Addisonian state induced by the use of mitotane there
would be a good chance of
recovery with fluid therapy and time, as the damage to the kidneys
tends to fall more into the "one
time insult" category rather than into a chronic progressive kidney
disease category. As the adrenal
glands recover from the effects of Lysodren over time, they will produce
corticosteroids again in
most, but not all, dogs. When this happens you will see the same signs
that were present previously,
such as increased drinking, increased urination, hair loss, thinning
of the skin, muscular weakness,
etc. It would be necessary to consider treatment again at that time.
There is some chance that the
current itchiness is due to calcinosis cutis, a secondary effect of
Cushing's disease, but it would be
good to rule out a secondary bacterial infection since there was a
period when it is likely that your
doxie's immune system wasn't working very well. If there was no response
to antibiotics it may be
necessary to think about administering corticosteroids. This seems
really odd to think about in a
patient suspected of having Cushing's disease, but it is not uncommon
for suppressed allergies or
other conditions responsive to corticosteroids to surface after treatment
for Cushing's disease. The
reason is that the dog was producing high levels of corticosteroids
due to the disease, which was
masking other symptoms. There would likely be a time when the symptoms
would be suppressed
again by natural recovery of the adrenal glands.
All of the above is based on the assumption that an Addisonian state
was induced by therapy for
Cushing's disease. The only way to really know if that happened is
to do ACTH testing to determine
if there is a response to the administration of ACTH. If a baseline
blood sample is drawn, then
ACTH administered (stimulates the adrenal gland) and blood drawn an
hour later shows no
response to the hormone, then it is very likely that the Lysodren completely
wiped out the ability of
the adrenal gland to produce cortisol, at least temporarily.
I understand why you might not want to do testing, especially now when
things have improved so
much. It would be necessary to do some type of testing prior to considering
starting Lysodren again.
It would be possible to start selegiline (Anipryl Rx) without further
testing and to monitor clinical
signs rather than lab values to assess success of therapy. At the present
time the best study that I can
find suggests that Anipryl is very effective in about 20% of the cases
of hyperadrenocorticism and
moderately effective in another 20%, so you would have to accept that
the odds of success are less
than 50%. You can always go back to Lysodren, or elect not to treat
for Cushing's disease, if
desired. If you do go back to Lysodren it would be probably be best
to do ACTH testing shortly
after starting treatment (maybe 72 hours) and then on frequent intervals
until a maintenance dosage
of Lysodren could be established. In any case, doing ACTH testing at
the first sign of loss of
appetite or vomiting would be a good idea.
I am hopeful that Darcy has continued to show progress in the kidney
values and that it has not been
necessary to administer Epogen (Rx) again. I am glad that you went ahead
with fluid therapy, as it
almost certainly helped in his recovery. I don't think it is
necessary to continue the fluid therapy at
this point if he has had another good test for kidney values (BUN <
30, Creatinine <1.5).
Mike Richards, DVM
2/2/2001
Cushing's
and dog's death from Kidney failure
Question: My dog was started on Anipryl for Cushing's disease
March 1998. He displayed many of the symptoms assoc. with the disease
(excessive drinking and urinating). He had one blood test at that
time which indicated that his liver enzymes were high. No other
testing was done.
This past summer my dog had several
UTI's and was treated with sulpha drugs. A blood test was taked in
July because he was vomiting yellow bile. His kidney function
was normal but his liver enzymes tested high.
Determined the sulpha drugs were causing the vomiting and the
medication was discontinued.
I had my dog back at the vet's
the middle of Oct. 2000 because I thought his teeth were giving him problems
(looked like he had a hard time chewing), sneezing a lot, had
a runny nose, and was losing weight. I also
mentioned to the vet that my dog would whine occasionally when
he tried to lay down ( vet thought maybe
arthritis). The vet checked his teeth, did not see any
problems and gave my dog a polyflex inj. No blood work
was done.
The end of November my dog was
vomiting yellow bile on and off for days. He would eat then 8 to
12
hours later vomit bile, stools were normal, no diarrhea, still
drinking water (not as much as he had in the past)
and urinating (but it seemed to take him awhile before he would
urinate). In the past several years he would
vomit bile for a day or two then be fine. The vet examined
him, thought it could be his liver and gave my dog a
polyflex and depomed inj. No blood work done. Before
he gave my dog the cortisone shot, I told the vet that
my dog had had a bad reaction to the depomed shot he gave him
a year ago for an ear infection. (My dog was
very agitated, restless, and panting heavily after receiving
the cortisone until he finally vomited 6 hours later
11/99.) I took my dog back to the vet the next day (11/29/00)
because he was now vomiting brown bile and his food right back up after
eating. He could also barely stand. The vet took a blood test
and then started my dog on sub-Q fluids. The vet called that night
to say his creatinine was high and that my dogs kidneys were
failing. A second blood test was taken a week later in
which his creatinine was still high. My dog was on
sub-Q fluids at home for three weeks before he died. I
made seven trips to the vet in that three week span.
Two trips because I thought my dogs teeth were bothering him.
It looked like he was having a hard time
chewing. Toward the end I finally realized it was not
the chewing food but the swallowing that was giving him
problems (swollen glands?). The vet checked his teeth
two different times did not see anything wrong but
pulled several teeth and gave him more cortisone. I thought
my dog was straining to have a bowel movement a
few days before he died, the vet checked his rectum said there
was blood in his stool but he was not backed
up. I took my dog back the next day because he was still
straining and the vet gave him an enema. My dog
had a lot of blood in his stool. I now realize my dog
was straining to urinate. He was drinking water and
urinating until the very end, not much of an appetite
though. What he ate he vomited right back up.
During the time period that my dog was vomiting the yellow
bile in November he would whine like he
did back in October when trying to lay down (abdominal pain,
stones, disc problems?).
My questions are the following:
What do Cushing's dogs generally die of? Do you give Cushing
patients more cortisone when
their bodies already produce too much steriods? Could the cortisone
have affected the blood test
results causing an elevation in the creatinine level?(A blood
test was not taken the first day I
brought my dog in which makes me question its validity.)
Do you treat kidney failure with
cortisone? Does the cortisone make a dog bleed internally?(My
dog did not have loose bloody
stools before he received the depomed injection) Should
my dog have been on IV fluids instead
of sub-Q fluids if his creatinine was high and had kidney failure?
What other factors could cause
the creatinine to be high? What other conditions could
cause my dog to vomit yellow bile? Could
he have had a urinary tract blockage (urinary or kidney stones)?
Should a urinary analysis have
been done? Could my dog have had a tumor? What would swollen
glands indicate?
Thanks, Susan
Answer: Susan-
It is likely that I am going to miss one of your questions in this answer,
so please feel free to ask for
additional clarification.
Cushing's disease causes a number of secondary problems in dogs. Recurrent
urinary tract infections
are not uncommon in dogs with Cushing's disease and some dogs with
this symptom have urinary
calculi (bladder stones or stones elsewhere in the urinary tract).
Infections of the skin and gums are
also possible as secondary problems due to immune suppression. Diabetes
mellitus commonly
occurs concurrently with Cushing's disease and they complicate each
other. About 15% of dogs
with Cushing's disease have adrenal gland tumors and some of these
are malignant. Among the 85%
of dogs who have pituitary-dependent Cushing's disease, about 20% will
eventually develop large
enough pituitary tumors to cause central nervous system disorders.
Dogs with Cushing's disease
frequently develop high blood pressure and an increase in blood clotting,
which leads to kidney
damage, heart damage and pulmonary embolisms. Gastrointestinal ulceration
can occur when
cortisol levels are high. Pancreatitis seems to be more common in patients
with Cushing's disease
based on our clinical experience. Since Cushing's disease is a geriatric
onset disorder in most cases
there are often times when another problem that was present causes
death before the complications
of Cushing's disease does.
If Cushing's disease is treated and the treatment is successful, some
of the above problems are less
likely, but other problems may occur. Some dogs have reactions to the
medications used to treat
hyperadrenocorticism and these are sometimes fatal. Once in a while,
treating for Cushing's disease
leads a sudden worsening of central nervous system signs in dogs. Because
dogs with Cushing's
disease are producing high levels of cortisol, this sometimes is masking
another disease, especially
skin disease and arthritis. Some dogs who are successfully treated
for Cushing's disease will need
care for these conditions and if it is difficult to achieve, there
is a risk of euthanasia. Some veterinary
clients will decide to euthanize their dogs due to the high cost of
treating Cushing's disease or the
inconvenience of returning for lab work repeatedly when mitotane (Lysodren
Rx) is used as the
treatment method, even though it is the most consistently effective
treatment.
We try not to use cortisones in dogs with Cushing's disease, but there
are times when a dog whose
Cushing's disease is well controlled will need corticosteroid administration
to treat other problems
that occur. Selegiline (Anipryl Rx) does not suppress cortisol levels
to the degree that mitotane does,
so we try harder not to use corticosteroids in patients we are treating
with this medication but we
have when it seemed really necessary.
It is not likely that a single corticosteroid injection would cause
kidney problems. Long term
exposure to high dosages of corticosteroids can cause kidney problems
through the development of
high blood pressure and blood coagulation problems which can induce
kidney disease.
Corticosteroids do cause ulcers in some dogs and this could cause intestinal
bleeding and it could
cause vomiting. Long term vomiting can occur for a number of reasons,
including gastrointestinal
disease, liver disease, parasitism, kidney disease, chronic pancreatitis,
cancer and central nervous
system disorders. In dogs with Cushing's disease, several of these
problems are likely to be present
and they can occur independently of the Cushing's disease, as well.
One problem that occurs with some Cushing's disease patients is immune
suppression, which might
lead to enlargement of the submandibular lymph nodes. It is also possible
that cancer was present in
the oral cavity, which also leads to increased size of the submandibular
lymph nodes.
Kidney damage occurs in many illnesses in which blood pressure gets
low or blood pressure gets
high and it can occur very quickly in the case of low blood pressure.
This is not an uncommon
problem when serious illness is present, especially in geriatric patients,
which seems to be the case
with your dog. It may have helped to use intravenous fluids rather
than subcutaneous fluids if this was
the case, but I do not know of a way to be sure of this.
When there are multiple problems present there is a tendency for one
to lead to a worsening of
another and for this process to continue to occur very quickly, leading
to a situation in which the
overall situation becomes overwhelming or at least seems that way.
In a geriatric patient this occurs
more quickly and when one of the problems becomes very severe there
is a tendency among people
making treatment decisions to give up and recommend euthanasia or to
adopt strategies such as
limiting pain and treating symptoms to keep patients as comfortable
as possible but not fighting the
problem all out, as might be done in a much younger patient with the
prospect of recovery and a
long life span, rather than recovery to the last previous level of
health, which often was not very
good. Age is not a decisive factor in this thinking, most of the time.
The level of pre-existing disability
is usually the decisive factor, especially when it is not clear that
even that can be obtained with
treatment. It really may have seemed obvious to your vet that your
dog had no chance of return to
an acceptable level of health. In that case, the real failure is not
managing to communicate that to you
in a way that you understood it. Sometimes I am not able to do that
for clients, so I know that it can
be a problem.
It is OK to ask long questions. Sometimes I miss some concerns in the
long notes and if that has
occurred, I will be happy to try to clarify whatever worries you.
Mike Richards, DVM
1/29/2001
Cushing's with
renal disease
Q: Dear Dr. Mike: We are sorry to bother you with
a second chapter about
our 16-year old Dachshund Clea, who had been diagnosed with Cushing's
in May. In our Aug. 30th message, we outlined the care we had been
providing
to her. Since that message was sent, we have done some further testing,
and
now have additional questions. On Wednesday, September 3, we did another
blood test. Bun was 96.8 and creatinine 2.81. Because of the high bun
reading,
she was put on fluids iv for the day (about 6 hours). Alkaline phosphatase
was
2791 and alt (sgpt) 231. These values seemed to have improved slightly
but we
were warned that they may reflect further loss of liver function rather
than
improvements. Glucose was 105.9 (normal reference range is shown to
be
77.0 - 125.0). We also did a blood count, and it reported values in
normal
ranges except for the platelet count, which was high at 799 x 10^9/L
(normal
reference range is shown to be 175 - 500). Our vet told us that this
was caused
by the Cushing's, and by her kidney disease. We have also been told
that one
effect of Cushing's is to cause clotting, with a serious risk of pulmonary
embolism,
which makes inserting iv's risky. We had another blood profile done
today
(Sept. 8th) on her kidney values. Bun = 88.5 mg/dl; creatinine = 2.79
mg/dl.
(Our vet decided not to put her on an iv today.) We also had her cortisol
level
tested on September 4th, and it was shown to be 7.1 mcg/dl (reference
values:
1.0 - 4.5). We have continued to feed her with a syringe. Because of
the high
bun count we use only the NF and clinicare. Targets per day are 200cc
of NF
(pureed with water) and 100cc's of clinicare. She has seemed somewhat
better
than last week and more interested in her normal activities, albeit
she is very weak
and falls down occasionally. We have been giving her baytril injections
im. Beginning
August 6, injections were given twice daily of 1cc (her weight was
then about 20 lbs).
On August 19, on the advice of our vet, we began giving injections
once daily (1.8 cc,
her weight having declined to 18 lbs) and continued until this past
Saturday (September 6),
when we stopped. We have read the pharmaceutical information provided
with the
drug, and understand from that information that the normal course for
baytril is ten
days, and that it does have adverse side effects, including vomiting
(it always had this
effect on Clea when given as a tablet), and because of how it works,
it should always
be given in two doses, not as a single dose. That pharmaceutical information,
however,
warned that baytril can have an effect on clotting, and her high platelet
count leaves us
concerned. In reviewing our records, we noted that the vomiting episode
which caused
us so much worry in late July, early August coincided with the administration
of the baytril.
At that time, she had high bacterial count in her urine and apparent
infections elsewhere,
so use of baytril made sense. Now, because of our concern about her
appetite, the
condition of her liver and the platelet count, we decided to stop administering
the baytril
until we had more information and could make an informed judgment about
the wisdom
of this treatment.
On Sept. 6th, the day we discontinued the baytril injections, her appetite
seemed to
have returned, at least partially; she has eaten a little solid food
on her own (for the
1st time in over a month), mostly of the high protein foods she likes
so much (sliced
roast beef from the delicatessen, and some canned dog food, baked chicken
and
rice (about 1/3 cup total of the combined foods)). Perhaps, the baytril
was a factor
in suppressing her appetite? She now weighs 17.6 lbs. What do you suggest
about
the baytril? Were we wrong to have administered it as we did for nearly
a month,
especially since she was on augmentin 21 days before that time? Should
we use it
as a preventative, or does that do more harm than good? It seemed a
bit odd that
the reason we were told not to use tagamet to help with Clea's digestion
is the inability
of the liver to break it down, yet doesn't breakdown of baytril in
the body use the
same system? And what do you suggest about the platelet problem? Our
vet said
something about aspirin, but what do you recommend? Will we have to
continue to
put Clea on iv's from time to time to help with the kidney disease?
Because she has
begun eating a little on her own, we have slowed down the syringe feeding,
which
she fights vigorously. She seems hungry, but the foods she nibbles
are all high in protein.
Should we put her back on lysodren in an effort to control the Cushing's
even though
her appetite is so poor? Should we consider half the previously prescribed
dose
(that is, 250 mg daily instead of 500 mg)? Do you think that would
be a good idea
considering her kidney problem? (Our questions and concerns about the
effect of
the lysodren therapy, possible overdose before she reached her maintenance
level
on lysodren, etc., were sent to you in our earlier message, so we won't
repeat them
again here.) Clea does really pretty well considering the illness and
her age. She sleeps
most of the day, but when she is awake she is alert and mobile (though
weak and
lame--her hindquarters give out every now and then). This past week,
she has started
barking again, with demands to go outside. She is alert to activities
outside in her yard,
and will sit before the screen door and watch for squirrels. Her breathing
is easy and
not labored, both when she is at rest and when she is active. (We have
noticed
occasional tremors in the past few days.) She is not experiencing any
discomfort, let
alone pain despite the weakness, so we still hope that there is something
we can do
for her. Well, this is a long list of problems, and the message got
a bit longer than we
meant it to. But we love this little dog dearly, and we really would
appreciate any
advice you can offer us. Many thanks. Tom and Maria
A: Tom and Maria-
We have used Baytril for long time periods when it seemed necessary.
So far, it
seems to cause less side effects than many antibiotics but that doesn't
mean it
couldn't be the cause of vomiting or inappetance in Clea. I am not
sure I followed
the rationale for antibiotic therapy but as you may have figured out
we get a lot of
email and it is difficult to keep track of individual cases.
I think I'd consider the use of one of the alternative therapies for
Cushing's disease.
Deprenyl is approved for this purpose now and ketaconazole is used
for control of
Cushing's as well. Both therapies are reported to be a little more
expensive than
mitotane (Lysodren Rx) therapy but that doesn't seem to be a major
concern on
your part. These products seem to have a little more safety margin
than Lysodren.
You might want to ask your vet about this.
I don't think I'd be too concerned about the platelet levels. Aspirin
will deactivate
platelet function but does not decrease platelet numbers, as far as
I know. I do not
think it would be harmful to use aspirin unless it caused gastrointestinal
upset but
I wouldn't be overly concerned about the possibility of clotting, personally.
Perhaps
your vet has a bad experience with this that I have managed to miss
in my practice
but so far, this has not been a big problem in our Cushing's patients,
to the best of
my knowledge and memory.
Monitoring the renal disease is important and continuing to treat symptoms
of
problems is a good idea. In complicated cases of hormonal disease it
can be
helpful to consider consulting with an endocrinologist or internal
medicine specialist.
Dr. Chiapella in Manassas is very good and the vets at the veterinary
school at
Blacksburg are also a good choice. This is not always necessary but
when I am
struggling with a case I like to get a second opinion on it --- even
if I'm doing the
best that can be done it is reassuring to hear that for the owner.
Good luck with this.
Mike Richards, DVM
Cushing's amended answer
Q: Your Q&A site was recommended to us by Leslie, whose dog
also has Cushing's. We have a number of questions, and apologize for
the
length of the explanation. Our dog (Cleopatra = "Clea") is a 16 year
old
(this month) longhaired dachshund who was diagnosed with Cushing's
in May
(dexamethasone suppression test give May 15). We had taken her to our
vet
because of persistent weakness, quite noticeable in an otherwise active
dog.
She had also begun to drink and urinate profusely, and had a huge appetite.
On
a blood panel done a week earlier, her liver enzymes were elevated,
but the test
was otherwise normal. On that test, the initial cortisol reading was
6.6 mcg/dl, and
the reading was elevated to 29.0 and 22.8 at 5 and 8 hours. She went
absolutely
flat after the test, and took about a week to recover. Because we had
been
unsuccessful with lysodren on two prior occasions in treating dogs
with Cushing's,
we tried to treat her condition with Eldepryl (Anipryl). The drug was
available
only in human form (for Parkinson's). Beginning May 20, we administered
1 5mg
capsule once a day until May 28, when we began administering 2 5mg
capsules
once a day, until a second dexamethasone suppression test was done
July 14th. The
readings for this test were 6.0 pre administration and 14.0 and 16.5
at the 5 and 8
hour marks. Again, Clea seemed to suffer greatly from this test. He
told us that the
drug had slightly changed the level of cortisol in her system, but
not enough and
recommended that we increase the dosage to the test dosage (4 5mg capsules
once
a day). We did try, but Clea is very resistant to taking pills, and
the capsules are
quite large, unsuitable for administration to a dog. A blood panel
also done at this
time disclosed that Clea's urea nitrogen had greatly increased, from
38 MG/DL in
May to 92 on July 14. Creatinine was 1.8 then, still in the range of
normal (although
her liver values were greatly elevated). This was diagnosed as a bladder
and/or kidney
infection. The bladder infection was confirmed by urine tests and a
culture. We
treated this with a liquid antibiotic called "augmentin." On July 22,
we had a sonogram
done, and this test reported a large adrenal tumor. Clea's liver was
enlarged and
opaque (as would be expected from Cushing's), and some indication of
kidney
deterioration. On the preceding Friday, Clea had tried to navigate
a flight of stairs,
but had fallen all the way to the bottom. Examination for possible
injury in this
situation, seemed to show only mild aggravation of an old lower back
injury,
but we wonder about that. In any event, she was by this time very weak,
and
with her liver and kidney problems, we decided against surgery. (One
of the
Cushing's dogs we had previously owned had had this surgery, but then
had
never gotten to his feet again. He died within a month from pneumonia.
With an
old dog, who had been weakened from the effect of the Cushing's, and
who had
a bunch of other problems, surgery seemed to be a poor choice.) Instead,
we
began to treat with lysodren (1/2 500mg tablet twice a day), as our
vet recommended.
These pills are dreadful. We were told that lysodren could be compounded
and
presented in liquid form at the required dosage, but we were never
able to find
someone who could do that. By the time of the sonogram, Clea's appetite
(which
had been very good up to that point) tapered off, and by the end of
the month,
ahe was not eating at all. We began to administer Lysodren on July
27 (250mg,
twice a day), although the information we had available to us then
indicated that
an adrenal tumor is very resistant to treatment with lysodren. An ACTH
stimulation
test given Aug. 6 showed that we had made some progress (pre test value
reported
as 2.0; post 2 hours, 7.8), and our vet advised us to increase the
Lysodren dose. But
Clea's kidney values had worsened (a blood test on that day showed
urea nitrogen
at 106.1 and creatinine at 2.63), she had stopped eating (and drinking
by that point)
and had begun vomiting. We were told that the vomiting was brought
on by the
deterioration of her kidneys (and probably other organs as well, particularly
the liver).
On August 10, we took her to the emergency room because of the vomiting.
She
was on iv fluids for about 2 days, and her kidney values improved (urea
nitrogen
from 107 (when admitted) to 51.3, Creatinine from 4.5 to 2.5), and
the vomiting
stopped. We also stopped giving her lysodren. When she came home with
us, we
began giving her baytril by intramuscular injection (1.8 cc once a
day) to control
the infections. Since August 13, we have fed Clea by syringe (with
Clinicare, a
Veterinary product like Ensure, and with pureed dietary foods such
as "EN-Formula"
(easy on the digestive system after vomiting and diarrhea episodes)
and more recently
"NF-Formula" (said to be easy on the kidneys)(both processed by Purina
CNM
and available by prescription through the Vet's office)), but she has
shown no interest
in eating solid food on her own, not even her most favorite foods,
although she has
taken a bite or two, here and there. In the past couple of days, we
have added small
quantities of pureed egg noodles for calories (with a couple of pureed
boiled chicken
livers). On August 20 and 21, we profused her kidneys a second time,
reducing the
Urea Nitrogen to 43.5 and the Creatinine to 1.96 (normal being reported
as [7-27]
and [.50-1.80] respectively), but still she will not eat. A blood test
administered last
week (August 27), showed her urea nitrogen at 49 and creatinine at
2.6 (Alkaline
phosphatase was shown at 2800 U/L and ALT (SGPT) at 385, about where
these
values have been for the better part of three months). We were alarmed
when
glucose was shown at 23 MG/DL, a large drop-off from the last time
this value
was tested (on Aug. 19), when it was 99.1. This was explained to us
as the effect
of allowing the blood sample to sit before being sent to the lab. But
we have never
seen this before, even in blood samples handled in the same way, so
it is alarming.
Clea is also noticeably weaker, and her eyes are a little red. She
drinks water on
her own and appears interested in her food bowl but just won't eat.
Her weight
has declined over three weeks from 20.2 lbs to 17.8 lbs.
We have a number of questions, which boil down to how to proceed. What
can we
do about her refusal to eat? Is there a better diet for her present
condition? Would
it hurt her to feed her the chicken livers (and gizzards) which she
likes? Is it possible
that this situation has been brought on or aggravated by a rapid decline
in the cortisol
levels in her system, even though she had reached her maintenance level?
If so, would
administration of prednisolone help her? The low dose dex suppression
test made her
go flat when it was done in July. Would it be helpful to try lysodren
again, even though
she is not eating? Is there a protocol for renal insufficiency that
we can follow for her?
Thanks for considering Clea's case. It took a while to set it out,
but we wanted you to
know as much as we could tell you. Any suggestions would be most appreciated.
Tom and Maria
A: Tom-
I didn't realize you had tried l-deprenyl when I sent the previous message.
It will
only work in pituitary dependent Cushing's disease so it is not surprising
that it did
not work well with an adrenal tumor present. Ketaconazole may alleviate
the cushingoid
effects of the tumor but will not stop the progression of the cancer
so it is also a
questionable choice. I can understand not wanting to do surgery for
adrenal gland
tumors, especially in an already compromised patient, but that is sometime
to consider,
as you know. Lysodren at dosages high enough to totally destroy the
adrenal tissue
has been advocated for treatment of adrenal gland tumors, as well.
This does produce
the opposite problem, hypoadrenocorticism or Addison's disease, and
it is necessary
to treat for this with appropriate medications, including Florinef (Rx) and possibly prednisone.
I think that I would be more worried about hypertension associated with
the Cushing's
disease leading to the secondary effects on the kidneys and possibly
causing some of
the other observed symptoms but I may not be aware of some detail of
the case that
makes your vets suspicious of this. Spread of the adrenal tumor to
the kidneys is also
possible and may be a contributing factor in their problems. Most vets
are still not
equipped to accurately measure blood pressure due to the cost of equipment
and
the learning curve associated with use of it.
It is acceptable to crush the Lysodren and load the powder into smaller
gelatin capsules
available at some pharmacies (you might have to search for one or ask
the pharmacist
or your vet to order them for you). This usually means giving a higher
number of capsules
than than the number of pills you were giving but the smaller size
may make it more
acceptable, anyway.
Do consider asking for referral to an internal medicine specialist.
I think that Cleopatra
sounds like a patient with a very complicated case of Cushing's disease
and it is often
best to seek the help of someone who deals with the most complicated
cases on a
more routine basis.
Mike Richards, DVM